JP2013213031A - ペプチドを含む医薬組成物 - Google Patents
ペプチドを含む医薬組成物 Download PDFInfo
- Publication number
- JP2013213031A JP2013213031A JP2013046756A JP2013046756A JP2013213031A JP 2013213031 A JP2013213031 A JP 2013213031A JP 2013046756 A JP2013046756 A JP 2013046756A JP 2013046756 A JP2013046756 A JP 2013046756A JP 2013213031 A JP2013213031 A JP 2013213031A
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- JP
- Japan
- Prior art keywords
- peptide
- pharmaceutical composition
- peptides
- amino acid
- injection
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
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Abstract
【解決手段】1種又は2種以上のペプチドを有効成分として含み、かつ塩基性アミノ酸及び/又は塩基を含む医薬組成物。塩基性アミノ酸がアルギニン、リシン、オルニチン、ヒスチジン、ヒドロキシリジン及びこれらの塩からなる群から選択される1種または2種以上の組合せであり、塩基が炭酸ナトリウム、炭酸カリウム、炭酸水素ナトリウム、炭酸水素カリウム、などからなる群から選択される1種または2種以上の組合せである。また、ペプチドは、T細胞エピトープペプチドである。
【選択図】なし
Description
[1] 1種又は2種以上のペプチドを有効成分として含み、かつ塩基性アミノ酸及び/又は塩基を含む医薬組成物。
[2] 塩基性アミノ酸がアルギニン、リシン、オルニチン、ヒスチジン、ヒドロキシリジン及びこれらの塩からなる群から選択される1種または2種以上の組合せである、[1]に記載の医薬組成物。
[3] 塩基が炭酸ナトリウム、炭酸カリウム、炭酸水素ナトリウム、炭酸水素カリウム、水酸化ナトリウム、水酸化カリウム、トリエタノールアミン、トロメタモール及びメグルミンからなる群から選択される1種又は2種以上の組み合わせである、[1]また[2]に記載の医薬組成物。
[4] ペプチドが、T細胞エピトープペプチドである、[1]〜[3]のいずれかに記載の医薬組成物。
[5] ペプチドが、2種以上のT細胞エピトープペプチドが直接又はリンカーを介して結合されたペプチドである、[1]〜[3]のいずれかに記載の医薬組成物。
[7] T細胞エピトープペプチドが、配列番号1、2、3、又は4に示すアミノ酸配列からなるペプチドの全種類のペプチドである、[4]または[5]に記載の医薬組成物。
[8] 腫瘍に対する免疫応答を誘導するための医薬組成物である、[4]〜[7]のいずれかに記載の医薬組成物。
[9] 癌を予防又は治療するための医薬組成物である、[8]に記載の医薬組成物。
[10] 非経口製剤の形態に剤形化されることを特徴とする、[1]〜[9]のいずれかに記載の医薬組成物。
[11] 非経口製剤が注射剤であることを特徴とする、[10]に記載の医薬組成物。
[12] [1]〜[11]のいずれかに記載の医薬組成物を凍結乾燥させた凍結乾燥製剤。
[14] 以下の工程を含む、[12]に記載の凍結乾燥製剤の製造方法;
(1)1種又は2種以上のペプチドを、塩基性アミノ酸及び/又は塩基を含む水溶液に溶解する工程;及び
(2)(1)で調製されたペプチド溶液を凍結乾燥する工程。
[15] ペプチドが、配列番号1、2、3、又は4に示すアミノ酸配列からなるペプチドの全種類のペプチドである、[14]に記載の凍結乾燥製剤の製造方法。
[16] 以下の(a)および(b)を含むキット:
(a)[12]に記載の凍結乾燥製剤;及び
(b)(a)の凍結乾燥製剤の再構成液。
[17] 以下の(a)および(b)を含むキット:
(a)[6]または[7]に記載の医薬組成物を凍結乾燥させた凍結乾燥製剤;及び
(b)配列番号5に示すアミノ酸配列からなるペプチドを含む(a)の凍結乾燥製剤の再構成液。
[18] さらに以下の(c)を含む、[16]または[17]に記載のキット:
(c)1種又は2種以上のアジュバント。
[19] 以下の(a)および(b)を含むキット:
(a)[1]〜[11]のいずれかに記載の医薬組成物;
(b)1種又は2種以上のアジュバント。
本発明の医薬組成物は、1種又は2種以上のペプチドを有効成分として含み、かつ塩基性アミノ酸及び/又は塩基を含む医薬組成物である。
1)アラニン(A)、グリシン(G)
2)アスパラギン酸(D)、グルタミン酸(E)
3)アスパラギン(N)、グルタミン(Q)
4)アルギニン(R)、リシン(K)
5)イソロイシン(I)、ロイシン(L)、メチオニン(M)、バリン(V);
6)フェニルアラニン(F)、チロシン(Y)、トリプトファン(W);
7)セリン(S)、スレオニン(T);および
8)システイン(C)、メチオニン(M)
また、本発明は、本発明の医薬組成物の製造方法を提供する。本発明の医薬組成物は、薬学的に許容される水性溶媒に塩基性アミノ酸及び/又は塩基を溶解して、塩基性アミノ酸及び/又は塩基を含む水溶液を作成した後、当該水溶液にペプチドを溶解し、当技術分野で公知の方法に従って製剤化することにより製造することができる。したがって、本発明の医薬組成物の製造方法は、塩基性アミノ酸及び/又は塩基を含む水溶液に、1種又は2種以上のペプチドを溶解する工程を含む。
本発明はまた、(a)本発明の医薬組成物の凍結乾燥製剤、及び(b)当該本発明の医薬組成物の凍結乾燥製剤の再構成液を含むキットを提供する。
注射剤用のペプチドとして、表1に記載のペプチドを合成した。表1に示すとおり、これらのペプチドの予測pIは5.2〜10.4の範囲であり、それぞれ溶解特性が異なることが予想された。これらのペプチドは、細胞障害性T細胞誘導能が確認されている腫瘍特異抗原由来ペプチドである。
注射用水:注射用水は日本薬局方に規定される製造用水を使用した。
表1に記載のペプチドの単味製剤を調製するために、注射用水1mLに、表1に記載のペプチドをそれぞれ投入した。室温で撹拌することにより投入したペプチドの全量を溶解させ、無色透明のペプチド単一溶液を調製した。その後、得られたペプチド溶液をろ過滅菌(0.22μmフィルター)して注射剤を得た。
炭酸ナトリウム 10水和物(Na2CO3・10H20)41mgを注射用水1mLに溶解し、炭酸ナトリウム含有注射用水を得た。比較例1で注射用水に溶解しなかったペプチドについて、各ペプチドの単味製剤を調製するために、炭酸ナトリウム含有注射用水1mLに、ペプチド−1、2、4、7、10をそれぞれ投入した。室温で撹拌することにより投入したペプチドの全量を溶解させ、無色透明のペプチド溶液を調製した。その後、得られたペプチド溶液をろ過滅菌(0.22μmフィルター)して注射剤を得た。
L−アルギニン40mgを注射用水1mLに溶解し、アルギニン含有注射用水を得た。比較例1で注射用水に溶解しなかったペプチドについて、各ペプチドの単味製剤を調製するために、アルギニン含有注射用水1mLに、ペプチド−1、2、4、7、10をそれぞれ投入した。室温で撹拌することにより投入したペプチドの全量を溶解させ、無色透明のペプチド単一溶液を調製した。その後、得られたペプチド溶液をろ過滅菌(0.22μmフィルター)して注射剤を得た。
炭酸ナトリウム10水和物41mg及びL−アルギニン40mgを注射用水1mLに溶解し、炭酸ナトリウム/アルギニン含有注射用水を得た。表1に記載のペプチドの単味製剤を調製するために、炭酸ナトリウム/アルギニン含有注射用水1mLに、表1に記載のペプチドをそれぞれ投入した。室温で撹拌することにより投入したペプチドの全量を溶解させ、無色透明のペプチド単一溶液を調製した。その後、得られたペプチド溶液をろ過滅菌(0.22μmフィルター)して注射剤を得た。
表1に記載のペプチドの配合注射剤を調製するために、実施例2と同様のアルギニン含有注射用水1mLに、表1に記載の10種のペプチドを1mgずつ投入した。各ペプチドを投入する毎にペプチドを全量溶解させて無色透明の溶液とし、その後、次のペプチドを投入した。10種全てのペプチドを溶解した後、得られたペプチド溶液をろ過滅菌(0.22μmフィルター)して注射剤を得た。得られた注射剤のpHは9.38であり、注射剤として適したpHの範囲内であった。
表1に記載のペプチド配合注射剤を調製するために、実施例1と同様の炭酸ナトリウム含有注射用水1mLに、表1に記載の10種のペプチドを2mgずつ投入した。各ペプチドの投入は実施例4と同様の方法で行った。10種全てのペプチドを投入した時点で無色透明の溶液が得られていたため、さらにペプチド−2を2mg投入したところ白濁が生じ、無色透明の溶液を得ることはできなかった。
表1に記載のペプチド配合注射剤を調製するために、実施例3と同様の炭酸ナトリウム/アルギニン含有注射用水1mLに、表1に記載の10種のペプチドを2mgずつ投入した。各ペプチドの投入は実施例4と同様の方法で行った。10種全てのペプチドを投入した時点で無色透明の溶液が得られていたため、さらにペプチド−2を2mg投入した。無色透明の溶液が得られたため、ろ過滅菌(0.22μmフィルター)により、注射剤を得た。得られた注射剤のpHは9.72であり、注射剤として適したpHの範囲内であった。
ペプチド−1、ペプチド−2、ペプチド−3、ペプチド−4を用いて、凍結乾燥製剤の製造を試みた。
実施例7において製造された凍結乾燥製剤は、癌治療用のペプチドワクチン製剤としての使用が想定される。癌治療用ペプチドワクチンは、癌免疫の誘導を促進するために、油性アジュバントと混合して乳化され、患者に投与される場合が多い。そのため、実施例7において製造した凍結乾燥製剤について、再溶解試験および再溶解液の乳化試験を行った。
Claims (19)
- 1種又は2種以上のペプチドを有効成分として含み、かつ塩基性アミノ酸及び/又は塩基を含む医薬組成物。
- 塩基性アミノ酸がアルギニン、リシン、オルニチン、ヒスチジン、ヒドロキシリジン及びこれらの塩からなる群から選択される1種または2種以上の組合せである、請求項1に記載の医薬組成物。
- 塩基が炭酸ナトリウム、炭酸カリウム、炭酸水素ナトリウム、炭酸水素カリウム、水酸化ナトリウム、水酸化カリウム、トリエタノールアミン、トロメタモール及びメグルミンからなる群から選択される1種又は2種以上の組み合わせである、請求項1または2に記載の医薬組成物。
- ペプチドがT細胞エピトープペプチドである、請求項1〜3のいずれか1項に記載の医薬組成物。
- ペプチドが2種以上のT細胞エピトープペプチドが直接又はリンカーを介して結合されたペプチドである、請求項1〜3のいずれか1項に記載の医薬組成物。
- T細胞エピトープペプチドが配列番号1、2、3、4、又は5に示すアミノ酸配列からなるペプチドのいずれか1種または2種以上のペプチドである、請求項4または5に記載の医薬組成物。
- T細胞エピトープペプチドが配列番号1、2、3、又は4に示すアミノ酸配列からなるペプチドの全種類のペプチドである、請求項4または5に記載の医薬組成物。
- 腫瘍に対する免疫応答を誘導するための医薬組成物である、請求項4〜7のいずれか1項に記載の医薬組成物。
- 癌を予防又は治療するための医薬組成物である、請求項8に記載の医薬組成物。
- 非経口製剤の形態に剤形化されることを特徴とする、請求項1〜9のいずれか1項に記載の医薬組成物。
- 非経口製剤が注射剤であることを特徴とする請求項10に記載の医薬組成物。
- 請求項1〜11のいずれか1項に記載の医薬組成物を凍結乾燥させた凍結乾燥製剤。
- 1種又は2種以上のペプチドを、塩基性アミノ酸及び/又は塩基を含む水溶液に溶解する工程を含む、請求項11に記載の注射剤である医薬組成物の製造方法。
- 以下の工程を含む、請求項12記載の凍結乾燥製剤の製造方法;
(1)1種又は2種以上のペプチドを、塩基性アミノ酸及び/又は塩基を含む水溶液に溶解する工程;及び
(2)(1)で調製されたペプチド溶液を凍結乾燥する工程。 - ペプチドが、配列番号1、2、3、又は4に示すアミノ酸配列からなるペプチドの全種類のペプチドである、請求項14に記載の凍結乾燥製剤の製造方法。
- 以下の(a)および(b)を含むキット:
(a)請求項12に記載の凍結乾燥製剤;及び
(b)(a)の凍結乾燥製剤の再構成液。 - 以下の(a)および(b)を含むキット:
(a)請求項6または7に記載の医薬組成物を凍結乾燥させた凍結乾燥製剤;及び
(b)配列番号5に示すアミノ酸配列からなるペプチドを含む(a)の凍結乾燥製剤の再構成液。 - さらに以下の(c)を含む請求項16または17に記載のキット:
(c)1種又は2種以上のアジュバント。 - 以下の(a)および(b)を含むキット:
(a)請求項1〜11のいずれか1項に記載の医薬組成物;
(b)1種又は2種以上のアジュバント。
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2016540779A (ja) * | 2013-12-06 | 2016-12-28 | ザ・ブロード・インスティテュート・インコーポレイテッド | 新生物ワクチン用製剤 |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10801070B2 (en) | 2013-11-25 | 2020-10-13 | The Broad Institute, Inc. | Compositions and methods for diagnosing, evaluating and treating cancer |
US11725237B2 (en) | 2013-12-05 | 2023-08-15 | The Broad Institute Inc. | Polymorphic gene typing and somatic change detection using sequencing data |
CN106456724A (zh) | 2013-12-20 | 2017-02-22 | 博德研究所 | 使用新抗原疫苗的联合疗法 |
SG10201902598VA (en) * | 2014-09-24 | 2019-04-29 | Aileron Therapeutics Inc | Peptidomimetic macrocycles and formulations thereof |
JP6781508B2 (ja) * | 2014-11-18 | 2020-11-04 | 塩野義製薬株式会社 | 安定化されたペプチド組成物 |
EP3234130B1 (en) | 2014-12-19 | 2020-11-25 | The Broad Institute, Inc. | Methods for profiling the t-cell- receptor repertoire |
EP3234193B1 (en) | 2014-12-19 | 2020-07-15 | Massachusetts Institute of Technology | Molecular biomarkers for cancer immunotherapy |
TWI806815B (zh) | 2015-05-20 | 2023-07-01 | 美商博德研究所有限公司 | 共有之gata3相關之腫瘤特異性新抗原 |
US11549149B2 (en) | 2017-01-24 | 2023-01-10 | The Broad Institute, Inc. | Compositions and methods for detecting a mutant variant of a polynucleotide |
CN110612115A (zh) | 2017-05-19 | 2019-12-24 | 学校法人庆应义塾 | 针对脑神经疾病的肽疫苗和肽疫苗组合物 |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2006526628A (ja) * | 2003-04-18 | 2006-11-24 | アイディーエム ファーマ,インコーポレイティド | Hla−a2腫瘍関連抗原ペプチドおよび組成物 |
JP2008530975A (ja) * | 2005-02-25 | 2008-08-14 | オンコセラピー・サイエンス株式会社 | Ttk、urlc10、またはkoc1ポリペプチドを発現する肺癌に対するペプチドワクチン |
JP2009292810A (ja) * | 2008-04-24 | 2009-12-17 | Immatics Biotechnologies Gmbh | ワクチン用のヒト白血球抗原(hla)クラスiまたはii分子に結合する腫瘍関連ペプチドの新規組成物 |
JP2010506826A (ja) * | 2006-10-17 | 2010-03-04 | オンコセラピー・サイエンス株式会社 | Mphosph1またはdepdc1ポリペプチドを発現する癌に対するペプチドワクチン |
JP2010519176A (ja) * | 2007-02-21 | 2010-06-03 | オンコセラピー・サイエンス株式会社 | 腫瘍関連抗原を発現する癌に対するペプチドワクチン |
WO2010095428A1 (en) * | 2009-02-18 | 2010-08-26 | Oncotherapy Science, Inc. | Foxm1 peptides and vaccines containing the same |
JP2010530846A (ja) * | 2007-06-01 | 2010-09-16 | アコロジックス インコーポレイティッド | 高温で安定なペプチド製剤 |
Family Cites Families (27)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2000037098A1 (en) * | 1998-12-22 | 2000-06-29 | Eli Lilly And Company | Shelf-stable formulation of glucagon-like peptide-1 |
CA2488404C (en) | 2002-06-06 | 2012-11-27 | Oncotherapy Science, Inc. | Genes and polypeptides relating to human colon cancers |
JP4406607B2 (ja) | 2002-08-26 | 2010-02-03 | オンコセラピー・サイエンス株式会社 | ペプチド及びこれを含む医薬 |
EP2267021B1 (en) | 2002-09-12 | 2015-02-18 | Oncotherapy Science, Inc. | KDR peptides and vaccines comprising the same |
TW200413725A (en) | 2002-09-30 | 2004-08-01 | Oncotherapy Science Inc | Method for diagnosing non-small cell lung cancers |
DK2095822T3 (da) * | 2005-02-28 | 2014-01-13 | Oncotherapy Science Inc | Epitoppeptider afledt af karendothelvækstfaktorreceptor-1 samt vacciner indeholdende disse peptider |
JP5095603B2 (ja) | 2005-07-27 | 2012-12-12 | オンコセラピー・サイエンス株式会社 | 結腸癌関連遺伝子tom34 |
CN103242428B (zh) | 2005-08-09 | 2015-04-15 | 肿瘤疗法.科学股份有限公司 | 用于hla-a2阳性人群的来自磷脂酰肌醇蛋白聚糖-3 (gpc3)的癌症排斥抗原肽以及含有该肽的药物 |
CN101108869B (zh) * | 2006-07-21 | 2010-06-02 | 海南德泽药物研究有限公司 | 一种芒果苷盐及其制备方法与用途 |
JP2008127283A (ja) * | 2006-11-16 | 2008-06-05 | Biseibutsu Kagaku Kenkyusho:Kk | ネコ伝染性腹膜炎用ワクチン |
GB0700523D0 (en) * | 2007-01-11 | 2007-02-21 | Insense Ltd | The Stabilisation Of Proteins |
JP5555952B2 (ja) | 2007-08-20 | 2014-07-23 | オンコセラピー・サイエンス株式会社 | Foxm1ペプチドおよびこれを含む薬剤 |
CN101835892B (zh) | 2007-08-20 | 2013-11-06 | 肿瘤疗法科学股份有限公司 | Cdca1肽和包含cdca1肽的药剂 |
CA2721800A1 (en) * | 2008-04-21 | 2009-10-29 | Nanobio Corporation | Nanoemulsion influenza vaccine |
TW201000119A (en) | 2008-06-10 | 2010-01-01 | Oncotherapy Science Inc | MYBL2 epitope peptides and vaccines containing the same |
TWI526219B (zh) | 2008-06-19 | 2016-03-21 | 腫瘤療法 科學股份有限公司 | Cdca1抗原決定位胜肽及含此胜肽的疫苗 |
TWI466680B (zh) | 2008-08-01 | 2015-01-01 | Oncotherapy Science Inc | Melk抗原決定位胜肽及含此胜肽的疫苗 |
TW201008574A (en) * | 2008-08-19 | 2010-03-01 | Oncotherapy Science Inc | INHBB epitope peptides and vaccines containing the same |
EP2362906B1 (en) | 2008-10-22 | 2015-04-08 | Oncotherapy Science, Inc. | Rab6kifl/kif20a epitope peptide and vaccines containing the same |
TWI500932B (zh) | 2008-12-05 | 2015-09-21 | Oncotherapy Science Inc | Wdrpuh抗原決定位胜肽以及含此胜肽之疫苗 |
TW201032820A (en) | 2008-12-16 | 2010-09-16 | Oncotherapy Science Inc | ELOVL7 epitope peptides and vaccines containing the same |
BRPI0923402A2 (pt) | 2008-12-24 | 2015-08-04 | Oncotherapy Science Inc | Peptídeos c10rf59 e vacinas incluindo os mesmos. |
KR20110134446A (ko) | 2009-03-04 | 2011-12-14 | 온코세라피 사이언스 가부시키가이샤 | Vangl1 펩티드 및 이를 포함한 백신 |
DK2408913T3 (en) | 2009-03-18 | 2017-03-06 | Oncotherapy Science Inc | NEIL3 PEPTIDES AND VACCINES CONTAINING THESE |
TW201124530A (en) | 2009-12-01 | 2011-07-16 | Oncotherapy Science Inc | IMP-3 oligopeptides and vaccines including the same |
TWI485245B (zh) | 2010-01-25 | 2015-05-21 | Oncotherapy Science Inc | 經修飾之melk胜肽及含此胜肽之疫苗 |
CA2857502C (en) * | 2011-11-30 | 2019-08-13 | 3M Innovative Properties Company | Microneedle device including a peptide therapeutic agent and an amino acid and methods of making and using the same |
-
2013
- 2013-03-08 WO PCT/JP2013/056429 patent/WO2013133405A1/ja active Application Filing
- 2013-03-08 KR KR20147028433A patent/KR20140138900A/ko not_active Application Discontinuation
- 2013-03-08 US US14/383,854 patent/US20150359864A1/en not_active Abandoned
- 2013-03-08 JP JP2013046756A patent/JP6159996B2/ja active Active
- 2013-03-08 SG SG11201405578TA patent/SG11201405578TA/en unknown
- 2013-03-08 EP EP13757952.0A patent/EP2823824A4/en not_active Withdrawn
- 2013-03-08 CN CN201380013184.9A patent/CN104168917A/zh active Pending
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2006526628A (ja) * | 2003-04-18 | 2006-11-24 | アイディーエム ファーマ,インコーポレイティド | Hla−a2腫瘍関連抗原ペプチドおよび組成物 |
JP2008530975A (ja) * | 2005-02-25 | 2008-08-14 | オンコセラピー・サイエンス株式会社 | Ttk、urlc10、またはkoc1ポリペプチドを発現する肺癌に対するペプチドワクチン |
JP2010506826A (ja) * | 2006-10-17 | 2010-03-04 | オンコセラピー・サイエンス株式会社 | Mphosph1またはdepdc1ポリペプチドを発現する癌に対するペプチドワクチン |
JP2010519176A (ja) * | 2007-02-21 | 2010-06-03 | オンコセラピー・サイエンス株式会社 | 腫瘍関連抗原を発現する癌に対するペプチドワクチン |
JP2010530846A (ja) * | 2007-06-01 | 2010-09-16 | アコロジックス インコーポレイティッド | 高温で安定なペプチド製剤 |
JP2009292810A (ja) * | 2008-04-24 | 2009-12-17 | Immatics Biotechnologies Gmbh | ワクチン用のヒト白血球抗原(hla)クラスiまたはii分子に結合する腫瘍関連ペプチドの新規組成物 |
WO2010095428A1 (en) * | 2009-02-18 | 2010-08-26 | Oncotherapy Science, Inc. | Foxm1 peptides and vaccines containing the same |
Non-Patent Citations (1)
Title |
---|
JOURNAL OF UROLOGY(AUA ANNUAL MEETING PROGRAM ABST, vol. Vol.185,No.4 Suppl., JPN6017005491, 2011, pages 710, ISSN: 0003503576 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2016540779A (ja) * | 2013-12-06 | 2016-12-28 | ザ・ブロード・インスティテュート・インコーポレイテッド | 新生物ワクチン用製剤 |
Also Published As
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EP2823824A4 (en) | 2015-09-16 |
CN104168917A (zh) | 2014-11-26 |
SG11201405578TA (en) | 2014-11-27 |
JP6159996B2 (ja) | 2017-07-12 |
WO2013133405A1 (ja) | 2013-09-12 |
US20150359864A1 (en) | 2015-12-17 |
EP2823824A1 (en) | 2015-01-14 |
KR20140138900A (ko) | 2014-12-04 |
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